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LLT1 and CD161 Expression in Human Germinal Centers Promotes B Cell Activation and CXCR4 Downregulation

Lookup NU author(s): Dr Lucy Walker, Dr Paul Milne

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Germinal centers (GCs) are microanatomical structures critical for the development of high-affinity Abs and B cell memory. They are organized into two zones, light and dark, with coordinated roles, controlled by local signaling. The innate lectin-like transcript 1 (LLT1) is known to be expressed on B cells, but its functional role in the GC reaction has not been explored. In this study, we report high expression of LLT1 on GC-associated B cells, early plasmablasts, and GC-derived lymphomas. LLT1 expression was readily induced via BCR, CD40, and CpG stimulation on B cells. Unexpectedly, we found high expression of the LLT1 ligand, CD161, on follicular dendritic cells. Triggering of LLT1 supported B cell activation, CD83 upregulation, and CXCR4 downregulation. Overall, these data suggest that LLT1-CD161 interactions play a novel and important role in B cell maturation within the GC in humans.


Publication metadata

Author(s): Llibre A, Lopez-Macias C, Marafioti T, Mehta H, Partridge A, Kanzig C, Rivellese F, Galson JD, Walker LJ, Milne P, Phillips RE, Kelly DF, Freeman GJ, El Shikh ME, Klenerman P, Willberg CB

Publication type: Article

Publication status: Published

Journal: Journal of Immunology

Year: 2016

Volume: 196

Issue: 5

Pages: 2085-2094

Print publication date: 01/03/2016

Online publication date: 01/02/2016

Acceptance date: 03/01/2016

Date deposited: 16/05/2016

ISSN (print): 0022-1767

ISSN (electronic): 1550-6606

Publisher: American Association of Immunologists

URL: http://dx.doi.org/10.4049/jimmunol.1502462

DOI: 10.4049/jimmunol.1502462


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Funding

Funder referenceFunder name
Obra Social La Caixa
University College London Hospitals/University College London National Institute for Health Research Comprehensive Biomedical Research Centre
National Institute for Health Research Biomedical Research Centre, Oxford
1U19AI082630-01National Institutes of Health/National Institute of Allergy and Infectious Diseases U19 Bio-Defense Program (National Institutes of Health/National Institute of Allergy and Infectious Diseases)
U19 AI082630National Institutes of Health/National Institute of Allergy and Infectious Diseases U19 Bio-Defense Program (National Institutes of Health/National Institute of Allergy and Infectious Diseases)
WT091663MAWellcome Trust Senior Fellowship

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